Open AccessIGFBP7 acts as a negative regulator of RANKL‐induced osteoclastogenesis and oestrogen deficiency‐induced bone loss
Author(s) -
Ye Chenyi,
Hou Weiduo,
Chen Mo,
Lu Jinwei,
Chen Erman,
Tang Lan,
Hang Kai,
Ding Qianhai,
Li Yan,
Zhang Wei,
He Rongxin
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12752
Subject(s) - osteoclast , rankl , bone resorption , osteoporosis , chemistry , wnt signaling pathway , osteoprotegerin , endocrinology , medicine , bone remodeling , growth factor , microbiology and biotechnology , osteoblast , in vivo , signal transduction , cancer research , receptor , in vitro , biology , biochemistry , activator (genetics)
Objectives Insulin‐like growth factor‐binding protein 7 (IGFBP7) is a low‐affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) via the Wnt/β‐catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis. Methods We used both in vitro and in vivo studies to investigate the effects of IGFBP7 on RANKL‐induced osteoclastogenesis and osteoporosis, together with the underlying molecular mechanisms of these processes. Results We show that IGFBP7 inhibited receptor activation of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, F‐actin ring formation and bone resorption, which was confirmed by using recombinant IGFBP7 protein, lentivirus and siRNA. The NF‐κB signalling pathway was inhibited during this process. Moreover, in a mouse ovariectomy‐induced osteoporosis model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity. Conclusions Taken together, these findings show that IGFBP7 suppressed osteoclastogenesis in vitro and in vivo and suggest that IGFBP7 is a negative regulator of osteoclastogenesis and plays a protective role in osteoporosis. These novel insights into IGFBP7 may facilitate the development of potential treatment strategies for oestrogen deficiency‐induced osteoporosis and other osteoclast‐related disorders.